Cyclopentanophenanthrene com-



United States Patent 3,138,584 CYCLOPENTANOPHENANTHRENE COM- POUNDS ANDPROCESS John A. Zderic, Mexico City, Mexico, assignor, by mesneassignments, to Syntex Corporation, a corporation of Panama No Drawing.Filed May 2, 1961, Ser. No. 107,049 21 Claims. (Cl. 260239) OR OR R1 R1R-N I Arc-N a do Esq 5 Body W05 In the above formulas R representshydrogen, alkyl or aralkyl groups containing up to 12 carbon atoms. Rrepresents hydrogen or an aliphatic hydrocarbon group, saturated orunsaturated, containing up to 8 carbon atoms such as methyl, ethyl,propyl, vinyl, propenyl, butenyl, ethinyl, propinyl and butinyl. Rrepresents hydrogen or the acyl radical of a hydrocarbon carboxylic acidof less than 12 carbon atoms. Z indicates a keto group, a B-hydroxygroup or a fi-hydrocarbon carboxylic acyloxy group of less than twelvecarbon atoms. The acyl groups are derived from hydrocarbon carboxylicacids of less than 12 carbon atoms, saturated or unsaturated, ofstraight, branched, cyclic or cyclic-aliphatic chain, aromatic and maybe substituted by functional groups such as hydroxy, alkoxy containingup to 5 carbon atoms, acyloxy containing up to 8 carbon atoms, amino,nitro or halogen. Typical ester groups are the acetate, propionate,butyrate, benzoate, cyclopentylpropionate, aminoacetate,,B-chloropropionate, hemisuccinate, enanthate, caproate,trimethylacetate, methoxyacetate, phenoxyacetate and phenylpropionate.Ac represents the acyl radical of a hydrocarbon carboxylic acid of lessthan 12 Patented June 23, 1964 carbon atoms as described above but ispreferably the cetyl or lower alkanoyl radical.

The novel compounds may be prepared by a process illustrated in part bythe following equation:

to m

IVa: R =hydrogen IVb: R =hydr0carbon CH 5:0 AcN lj IOH m USE Inpracticing the process outlined above, the starting compound I isproduced by reacting 115, 12,8-dihydroxytigogenin, described by Djerassiet al., J. Org. Chem. 16,

1278 (1951), with lead tetraacetate in an inert solvent such as benzeneto form 11,12-seco-5a,22a-spirostan-3/3- ol-l 1,12-dial. The dialdehydeis then reacted with ammonia in ethanol solution thereby yielding aSchifr base type intermediate which is then treated with lithiumaluminum hydride in tetrahydrofuran to yield lla-aza-C-homo-a,22a-spirostan-3fl-ol. Degradation of the spiroketal side chain isthen effected by conventional procedure as by reaction with aceticanhydride at about 200 (1., oxidation of the resulting pseudo-compoundto the diosone and alkaline hydrolysis and acetylation of the latterthus forming l1a-N-acetyl-C-homo-A -allopregnen-3fi-ol-20-one acetate.The degradation of the side chain may be preceded by acylation,preferably acetylation, thus forming 3/3-acetoxy-11a-N-acetyl-C-homo-5a,22a-spirostan which may then be subjected to degradation of the sidechain to form the lla-N-acetyl-C-homo- A -allopregnen-3,3-ol--oneacylate.

A hydroxyl group is then introduced at C-17oz by first epoxidizing thedouble bond at C-16,17, preferably by reaction with aqueous alkalineperoxide in which case the acyloxy group at 0-3 is saponified and thereis formed 11a N acetyl C homo 16a,17a-epoxy-allopregnan- 3fi-ol-20-one.Reacylation with a hydrocarbon carboxylic acid anhydride of less than 12carbon atoms, preferably acetic anhydride, affords11a-N-acetyl-C-homo-16a,17aepoxy-allopregnan-313,01-20-one acylate. Thelatter compound may also be prepared by epoxidizing the 16,17- doublebond of 1la-N-acetyl-C-homo-A -allopregnen-3fiol-20-one acylate witht-butylhydroperoxide [see Yang, J. Am. Chem. Soc. 80, 5845 (1958)] whichreaction does not affect the 3B-acyl group. The resulting '3fi-acyloxy-11a N acetyl C homo 16u,17a epoxy allopregnan20-one is reacted withhydrogen bromide to form the l6fi-bromo-17a-hydroxy grouping which upontreatment with Raney nickel results in reductive debromination and thereis formed the starting compound lla-N-acetyl-C-homo-allopregnane-3/3,17a-diol-20-one-3-acylate (1). Upon treatment ofthe latter compound with a double metal hydride such as sodiumborohydride there is formed 11a- N acetyl C homo allopregnane 313,l7a,20triol (II). The triol is then reacted with either sodium periodate inaqueous methanolic tetrahydrofuran or lead tetraacetate in acetic acidto obtain lla-N-acetyl-C-homo-androstane-3fi-ol-17-one (III) which upontreatment with sodium borohydride is transformed into lla-N-acetyl-C-homo-androstane-3/8,17/3-diol (IVa). Either of the foregoing compoundscan be esterified by conventional methods with hydrocarbon carboxylicacids of less than 12 carbon atoms, to afford the 3,8-acylate oflla-N-acetyl-C- homo-androstan-3fi-ol-l7-one or the 3,8,17fi-diacylateof 1 la-N-acetyl-C-homo-androstane-35,17 3-diol.

For introduction of the l7fi-hydroxy-l7a-aliphatic hydrocarbon grouping,11a-N-acetyl-C-homo-androstan-35- ol-17-one (III) is reacted withexactly two equivalents of an aliphatic magnesium halide such as methylmagnesium bromide, ethyl magnesium bromide, vinyl magnesium bromide orethinyl magnesium bromide in a solvent such as tetrahydrofuran to formthe lla-N-acetyl-C- homo-lh-aliphatic hydrocarbonsubstituted-androstane- 318,1713-diol (IVb). Oxidation of this lattercompound with pyridine-chromium trioxide complex at room temperatureaffords 11a-N-acetyl-C-homo-l7a-aliphatic hydrocarbon substitutedandrostan-l7 3-ol-3-one (V). Esterification of the tertiary hydroxygroup at C-l7 may then be etfected in benzene solution with hydrocarboncarboxylic acid anhydride of less than 12 carbon atoms in the presenceof p-toluenesulfonic acid to form lla-N- acetyl-C-homo-Hot-aliphatichydrocarbon substituted androstan-17fl-ol-3-one-17-acylate (VI).

Upon reaction of 11a-N-acetyl-C-homo-androstan-lifio1-17-one (III) withan excess of an aliphatic magnesium halide as described above, there isformed lla-aza-C- homo-17a-aliphatic hydrocarbon substituted androstane-3,3,17,8-diol (VII), which upon oxidation with chromic acid in pyridinesolution is transferred into lla-aza-C- homo-17a-aliphatic hydrocarbonsubstituted androstanl7B-ol-3-one (VIII). Conventional esterification ofthe latter compound with hydrocarbon carboxylic acid anhydrides of lessthan 12 carbon atoms affords the corresponding lla-N-acyl-IZB-olderivatives (V) whereas csterification with the hydrocarbon carboxylicacid anhydrides in an inert organic solvent and in the presence ofp-toluenesulfonic acid provides the corresponding Ila-N-acyl-17B-acylates (VI).

The novel lla-N-alkylated-C-homo compounds of the present invention areprepared by a process illustrated by the following equation:

m mud;

OR OH WW5 to.

XIV

In the above formulas Ac, R and R have the same meaning as set forthpreviously. R indicates an alkyl or aralkyl group containing up to 12carbon atoms; R represents a lower alkyl group and X represents ahalogen such as iodine, chlorine or bromine.

In practicing the process outlined above, an lla-N-acyl-C-homo-allopregnan-Iifl,17a-diol-ZO-one-3B-acylate, preferably11a-N-acetyl-C-homo-allopregnane-SB,17a-di0l-20- one-3-acetate (I) isrefluxed with lithium aluminum hydride in an inert solvent such astetrahydrofuran for a period of time of the order of 5 hours to formlla-N-ethyl- C-homo-a1lopregnane-3fi,17a,20-triol (IX), which uponcleavage with sodium periodate or lead tetraaoetate affords1la-N-ethyl-C-homo-androstan-3B-ol-l7-one (X). Treatment of thiscompound with a lower alkyl, alkenyl or alkinyl magnesium halide such asfor example methyl magnesium bromide, vinyl, or ethinyl magnesiumbromide, in an inert solvent such as tetrahydrofuran, affords thecorresponding Not-aliphatic hydrocarbon substituted-11a-N-ethyl-C-homo-androstan-3p,17,3-diol (XI). Treatment of this lattercompound with an oxidizing agent such as pyridine-chromium-trioxidecomplex provides the corresponding 3-keto compound (XII). Acylation ofthe thus formed Hot-aliphatic hydrocarbon substituted 11a-N-ethyl-C-homo-androstan-17B-ol-3-one as by reaction with hydrocarboncarboxylic acid anhydride of less than 12 carbon atoms in the presenceof p-toluenesulfonic acid furnishes the Hot-aliphatic hydrocarbonsubstituted-11a- N-ethyl-C-homo-androstan-17fi-ol-3-one-17-acylate.

The same method when applied to a 3,17-diol such as the Not-aliphatichydrocarbon substituted-1la-N-ethyl-C- homoandrostane-3fi,l7,B-dio1furnishes the 3,8,175-diacylate; whereas when p-toluenesulfonic acid isabsent, selective acylation at C3,B is efifected thus furnishing the3,8- acylate of this last mentioned diol.

Upon treatment of 1121-1 -ethyl-C-homo-androstan-3B- ol-17-one (X) withsodium borohydride, there is formed the diol (XIII) which can beconventionally esterified to yield the diester oflla-N-ethyl-C-homo-androstane-3[3, 17fi-diol.

Quaternary ammonium salt derivatives of all of the N-alkylated compoundsare prepared by conventional reaction with an alkyl or aralkyl halidecontaining up to 12 carbon atoms in a solvent such as a ni-troalkane.Thus for example, 1la-N-ethyl-C-homo-androstan-35-01-17-one dissolved innitromethane is reacted with methyl iodide to afford the methoiodide of11a-N-ethyl-C-homo-androstan-3B-ol-17-one.

There are obtained other N-acylated and N-alkylated compounds bysubstituting for the N-acetyl group other acyl radicals derived fromhydrocarbon carboxylic acids of less than 12 carbon atoms of the typedescribed previously. Thus there are obtained N-acylated and N-alkylated compounds containing up to 12 carbon atoms such asN-propionyl, N-butyryl, N-benzoyl and the corresponding N-propyl,N-butyl and N-benzyl derivatives.

The following examples serve to illustrate but are not intended to limitthe scope of the invention:

Example I To a mixture of 8.1 g. of 11,8,IZfl-dihydroxy-tigogenindescribed by Djerassi et al., J. Org. Chem. 16', 1278 (1951), 140 ml. ofglacial acetic acid and 210 ml. of thiophenefree benzene, 12.1 g. oflead tetraacetate were added and the mixture was stirred at roomtemperature for 5 minutes. 200 ml. of water containing 100 g. of sodiumacetate and 4 g. of sodium iodide were added, the color was dischargedby the addition of 80 ml. of saturated aqueous sodium thiosulfatesolution and the product extracted twice, using each time 200 ml. ofethyl acetate. The pooled extracts were washed with aqueous sodiumbicarbonate and water, dried over anhydrous sodium sulfate andevaporated to dryness. The residue was crystallized from a mixture of 60ml. of methanol and 12.5 ml. of water to afford11,1Z-SfiCOrSCQZZfl-SPII'OStflIl-t)[3'01"11, 12-dial.

A mixture of -5 g. of the dialdehyde and 250' ml. of ammonia-saturatedethanol was refluxed during hours. Upon evaporation of the solvent, acrystalline residue was obtained which was refluxed with 2.5 g. oflithium aluminum hydride, in mixture with 250 ml. of tetrahydrofuranduring hours. The excess of hydride was then decomposed by carefuladdition of acetone, then a small amount of saturated aqueous sodiumsulfate solution and finally solid anhydrous sodium sulfate were added.The solid was collected by filtration and the filtrate evaporated todryness under reduced pressure. Crystallization from aqueous ethanolyielded 11a-aza-C-homo-5a,22a-spirostan-3fi-ol.

Example ll 4 g. of the latter compound was heated with 20 ml. of aceticanhydride in a sealed tube at 200 C. for 55 minutes; it was then cooled,the excess of anhydride was hydrolyzed by addition of 8 ml. of water andthe mixture was treated with 2 g. of chromium trioxide in ml. of 80%acetic acid; after stirring for three hours at room temperature, themixture was diluted with water, extracted with ether and the extract waswashed with water, dried over anhydrous sodium sulfate and the ether wasevaporated. The residue was mixed with 200 ml. of 60% acetone containing2 g. of potassium hydroxide and refluxed for 5 hours, then concentratedto a small volume, cooled, diluted with water and extracted with ether.The extract was washed several times with water, dried over anhydroussodium sulfate and evaporated to dryness. Upon conventional acetylation,followed by recrystallization from acetone hexane, there was produced3,8-acetoxy-lla- N-acetyl-C-homo-A -allopregnen-ZO-one.

Example 111 2 g. of 11a aza C homo-5a,22a-spirostan-3,8-01 (described inExample I) was treated with 2 ml. of acetic anhydride in 10 ml. ofpyridine at room temperature. The mixture was allowed to stand overnightand was then diluted with water, the solid was collected by filtration,washed with water, dried and recrystalized from acetonehexane thusaffording 3fi-acetoxy-1la-N-acetyl-c-homm Sa,22 a-spirostan. The lattercompound was then treated with acetic anhydride at 200, the resultingpseudo-sapogenin oxidized to the diosone and was then'treated withpotassium hydroxide and reesterified as described in Example II to thusyield 3B-acetoxy-1la-N-acetyl-C-hOmO- A -allopregnen-20-one, identicalwith the compound obtained in Example II.

Example IV 2 g. of 3/3-acetoxy-11a-N-acetyl-CrhornorA rallopregnen-20-one in 12 ml. of benzene, 1.0 m1. of Triton B (benzyltrimethylammonium hydroxide, Midwest Laboratories Inc.) and 1.2 ml. oft-butylhydroperoxide (Lucidol Division, Wallace and Tiernan, Inc.) werereacted at room temperature overnight. The mixture was then diluted withwater, saturated with sodium chloride and extracted repeatedly withether. The combined extracts were dried over anhydrous sodium sulfateand evaporated to dryness. By crystallization from acetone-hexane,3,8-acetoxy-l1a-N- acetyl-l6a,17a-oxido-C-homo-allopregnan-20=.one wasobtain'ed.

Example V 1.4 g. of the above compound in 16 ml. of glacial acetic acidwere treated with 3 ml. of acetic acid saturated with dry hydrogenbromide, stirring at room temperature for 1.5 hours. The mixture wasthen diluted with ice water and the bromohydrin which precipitated wascollected by filtration, washed with water and refluxed with 10 g. ofRaney nickel in 500 ml. of methanol for 30 minutes. The nickel wasremoved by filtration, the filtrate was evaporated to dryness and theresidue crystallized from acetonehexane thus furnishing 38-acetoxy-1la-acetyl-C-homoallopregnan-17a-o1-20-one.

Example VI To 10 ml. of methanol containing 0.4 g. of lla-N-acetyl- Chomo-allopregnan-3p,17a-di0l-20-one 3-acetate was added 0.4 g. of sodiumborohydride, 0 .5 ml. of water and 2 ml. of dioxane, the resultingmixture was then refluxed for 5 hours, acidified with acetic acid andevaporated to a volume of 5 ml. Elution with water provided acrystalline product which was washed with water, dried andrecrystallized from acetone to provide lla-N-accty'l-C-homo allopregnan36,17a, 20 triol; M.P. 238-240=; [a] .-38 (pyridine).

Example VII Treatment of the above product (210 g.) in 4 ml. of aceticacid with 400 mg. of lead tetraacetate for 20 minutes at roomtemperature provided a crystalline product after dilution with water.Recrystallization from methanol gave lla-N-acetyl Chomo-androstan-Sdol-l7-one, M.P. 279280; [a] +172.6. The same productcould be obtained from its precursor by treatment with 2 equivalents ofsodium periodate in liquid methanolic tetrahydrouran.

Example VIII 1 g. of the above l7-ketone in 200 ml. of tetrahydrofuranwas added to 200 ml. of 4 N ethereal methyl magnesium bromide. Themixture was then heated (calcium chloride for protection) for 48 hoursat reflux temperature and finally decomposed with aqueous ammoniumchloride. After extraction with ethyl acetate and waterwashing of theextracts followed by solvent evaporation there was provided a residuewhich was crystallized from ether-acetone to providel7a-methyl-1la-aza-C-homo-androstane-3B,l7fl-diol.

Example IX By the same general method described in Example VIII, butemploying ethynyl magnesium bromide or vinyl magnesium bromide therewere also prepared Not-ethynyl and l7a-vinyl-lla-aza-C-homo-androstaneStine-diol.

Example X 1 g. of chromium trioxide was added slowly with agitation andcooling to 20 parts of dried pyridine. A solution of 1 g. ofl7a-methyl-l1a-aza-C-homo-androstane- 3,8,l7B-diol was added dropwiseand the resulting mixture was allowed to stand at room temperatureovernight; ethylacetate was then added to the reaction mixture and theproduct filtered through celite and eventually through a short aluminacolumn. The resulting eluates were then evaporated to dryness and theresidue was recrystallized from acetone-hexane to provide Hot-methyllla-aza-C-homo-androstan- 17fi-ol-3-one.

Example XI By the method of Example X there were also preparedl7a-ethynyl and 17a-vinyl-lla-aza-C-homo-androstan-17fi-ol-3-one.

Example XII 1 g. of 17a-methyl-lla-aza-C-homo-androstan-l75-01- 3-one in50 ml. of acetic acid and 10 m1. of acetic anhydride was treated with 1g. of p-toluenesulfonic acid and the mixture was left at roomtemperature for 30 hours. Following this period the mixture was pouredinto Water and the excess of anhydride was hydrolyzed. The solution waspoured into water and the excess of anhydride was hydrolyzed. Thesolution was then made alkaline with solid sodium hydroxide whereafterisolation of the product by ethyl acetate extraction andrecrystallization of the residue from acetone-ether gave17amethyl-lla-N-acetyl-C-homo-androstan-17a-ol-3-one l7- acetate. Thesame general method also provided the N-acetyl 17B-acetate derivative ofthe 3-ketone prepared in Example XI.

Example XIII By the general method of Example VIII, by using exactly 2equivalents of methyl magnesium bromide there was obtained 17mmethyl-11a-N-acetyl-C-homo-androstane-3fl,l7fl-diol. By similarprocedure but employing the corresponding vinyl magnesium bromide andethynyl magnesium bromide there were obtained the corresponding11a-N-acetyl-C-homo-androstane-3p,l7e-diol substituted in thel706-POSlllll by ethynyl or vinyl.

Example XIV A solution of one part of sodium borohydride in 3 parts ofwater was added to one part of the l7-ketone obtained in Example VIIdissolved in 120 parts of methanol. The mixture was allowed to stand atroom temperature for 16 hours whereupon the excess reagent wasdecomposed with acetic acid. The solution was concentrated to a smallvolume, diluted with water and the resulting precipitate collected.Recrystallization from ethyl acetate-hexane provided 11aN-acetyl-C-homo-androstane-35,175- diol.

8 Example XV 750 mg. of the above product was treated with leadtetraaeetate following the procedure described in Example VII yieldinglla-N-ethylC-homo-androstan-35-01- 17-one.

Example XVII l g. of the foregoing steroid was reacted with methylmagnesium bromide, such as described in Example VIII, thus furnishingl7a-methyl-1 la-N-ethyl-C-homo-androstane-3}9,17fi-diol.

Example XVIII Upon reaction of 1la-N-ethyl-C-homo-androstan-3{3-ol-l7-one with ethynyl magnesium bromide or vinyl magnesium bromidefollowing the method described in Example VIII, there were obtained17a-ethynyl-11a-N-ethyl- C-homo-androstane-BB,l7fi-diol and17a-vinyl-1la-N-ethyl-C-homo-androstane-3/i,17fl-diol.

Example XIX A solution of l g. ofl7a-methyl-lla-N-ethyl-C-homoandrostane-3;8,17}8-di0l in 20 cc. ofpyridine was treated following exactly the procedure described inExample X and 17a-methyl-1la-N-ethyl-C-homo-androstan-175-01-3- one wasobtained.

By the same method were oxidized: 17a-ethynyl-l1a-N-ethyl-C-homo-androstane-3a,l7a-dio1 and l7a-vinyl-1la- N-ethyl Chomo-androstane-3B,l7 3-diol to their corresponding 3-ketones: 17aethynyl-1la-N-ethyl-C-homoandrostan 17/3 ol-3-one andl7a-vinyl-lla-N-cthyl-C- homo-androstan-l7,8-ol-3-one.

Example XX 750 mg. of17a-rnethyl-l1a-N-ethyl-C-homo-androstanl7a-ol-3-one were acetylated inaccordance with Example XII andl7a-methyl-11a-N-ethyl-C-homo-androstan-l7,3- ol-3-one 17/3-acetate wasobtained.

According to the same procedure were acetylated the two last compoundsof Example XIX furnishing corresponding 17a ethynyl11a-N-ethyl-C-homo-androstanol-3-one-l7fi-acetate, and17a-viuyl-11a-N-ethyl-C- homo-androstan-17fi-o1-3-one-17}8-acetate.

Example XXI 500 mg. of l1a-N-ethyl-C-homo-androstan-3[3-01-17-oneobtained according to Example XVI was reduced with sodium borohydridefollowing the procedure described in Example XIV yieldingl1a-N-ethyl-C-homo-androstan- 313,17B-di0l.

Example XXII 1 g. of l7a-methyl-N-acetyl-C-homo-androstame-3 8,17B-

-diol in 30 cc. of pyridine was treated with 2 cc. of acetic anhydride.The reaction mixture was kept overnight at room temperature. Ethylacetate was added and the solution washed successively with dilutedhydrochloric acid, a 5% sodium bicarbonate aqueous solution and water.The extract was dried over anhydrous sodium sulfate and evaporated todryness. The solid residue was recrystalacetates indicated:

Starting compound Products17a-methyl-lla-N-ethyl-O-hornoandrostane-3B,17B-diol.

11a-N-acetyLC-homo-androstan- 3B-o1-17-0ne.

lla-N-ethyl-C-homo-androstan- 3B-ol-17-one.

11aNacetyl-Qhomo-audrostan- 3fi-acetate of 17a-methy1-11a-N-ethy1-C-h0mo-androman-35,17,3-

diol.

' androstan-SB-ol-H-one. 35'acetate oflla-Nfethyl-C-homoandrostan-3B-ol-17pne. 3,9,175-diacetate oflla'N-acetyl-C- homo-androstane-3fl,17fl-di01.

Example XXIII Following the procedure described in Example XII wereacetylated the starting materials indicated furnishing the correspondingproducts set forth below:

Starting materials 17a-methy1-1la-N-acetyl-C-homoandrostane-3B,l7B-diol.

17a-methy1-1la-N-ethyl-C-homoandrostane-35,17B-diol.

17a-vinyl-lla-N-ethyl-C-homoandrostane-3fi,17B-diol.

Products 35,17B-diacetate of 17a-methyl-11a- N-ethyl-C-homo-androstane-3,8,l7B-diol.

3flJ7fi-diacetate of IM-ethynyl-ll-a N -ethyl-O-homo-androstaneseam-(1101.

318.17fi-diacetate of l7a-vinyl-11a- N-ethyl-C-homoandrostane- ExampleXXIV 17-one.

Following the same procedure were treated the starting compounds namedhereafter, furnishing the corresponding methoiodides set forth below:

Starting compounds 17a-methy1-1la-N-ethyl-O-homoandrostane-SB,17fi-d101.

17a-vinyl-11a-N-ethyl-O-homoandrstan-17B-ol-3-one.

17a-methyl-l1a-N-ethyl-C-homoandrostan-l7fl-ol-3-one-l76- acetate11a-N-ethyl-C-homo-androstan-3fl,

1713-dio1.

3,3, 17fl-diacetoxy-17a-Methyl-11a- N-ethyLC-homo-androstane.

Products 10 I claim: 1. A compound of the following formula:

wherein R is selected from the group consisting of hydrogen landaliphatic hydrocarbon containing up to eight carbon atoms; R is selectedfrom the group consisting of hydrogen and hydrocarbon carboxylic acyl ofless than 12 c rbon at m Z is e e d from he oup Consisting o ket o,fl-hydroxy and fl-hydrocarboncarboxylic acyloxy of less than 12 carbonatoms and Ac represents the acyl radioal of a hydrocarbon carboxylicacid of less than 12 carbon atoms.

2. 1 la-N-acetyl-C-homo-androstane-Sfl,17B-diol.

3. 17a-methyl-1la-N-acetyl C homo androstan-l7fiol3-one.

4. 17a-ethinyl-11a-N-acetyl C homo androstan-Upol-3-one.

5. The hydrocarbon carboxylic acid ester of less than 12 carbon atoms ofl7a-lower alkyl-1=1 a-N-acetyl-C-hom0- androstan-17B-ol-3-one.

6. The hydrocarbon carboxylic acid ester of less than 12 carbon atoms of17a-lower alkyl-lla-N-acetyl-C- homo-androstane-3,8,17,8-diol.

7. A compound selected from the group consisting of the followingformula:

and the lower alkyl quaternary ammonium halides thereof wherein R isselected from the group consisting of hydrogen, alkyl and aralkylcontaining up to 12 carbon atoms; R is selected from the groupconsisting of hydrogen and aliphatic hydrocarbon containing up to eightcarbon atoms; R is selected from the group consisting of hydrogen andhydrocarbon carboxylic acyl of less than 12 carbon atoms; and Z isselected from the group consisting of keto, B-hydroxy and fl-hydrocarboncarboXylic acyloxy of less than 12 carbon atoms.

8. lla-aza-C-homo-androstan-SB,17,8-diol.

9. 11a-aza-C-homo-androstan-l7fi-ol-3-one.

10. 17a-lower alkyl-11a-aza-C-homo-androstan-17,8-01- 3-one.

11. The hydrocarbon carboxylic acid ester of less than 12 carbon atomsof 17a-1OW61 alkyl-lla-aza-C-homoandrostan-17fi-ol-3-one. v

12. 17oc-10W6I alkyl-1la-N-ethyl-C-homo-androstane- 3fi,17,8-diol.

-13. The hydrocarbon carboxylic acid ester of less than 12 carbon atomsof 17a-lower alkyl-1la-N-ethyl-C-homoandrostane-3 3,l7/3-diol.

14. The methoiodide of 1la-N-ethyl-C-homo-androstane-3B,l7fi-diol.

15. The methoiodide of -17a-methyl-1la-N-ethyl-C-homo-androstan-17B-ol-3-one.

11 12 16. The hydrocarbon carboxylic acid ester of less than 19. Acompound selected from the group consisting of 12 carbon atoms of themethoiodide of 17a-methyl-11athose of the following formula:

N-ethyl-C-homo-androstan-175-01-3-one.

17. A compound of the following formula: I

and the lower alkyl quaternary ammonium halide thereof wherein R isselected from the group consisting of hydro gen, alkyl and aralkylcontaining up to 12 carbon atoms; 15 and R is selected from the groupconsisting of hydrogen and hydrocarbon carboxylic acyl of less than 12carbon J n m m m 2 atoms. wherein R 1s selected from the groupconsisting of hy- 2O 11a N eth 1 C hom0 androstan 3fl ol 17 one drogenand hydrocarbon carboxylic acyl of less than 12 The methyoiodide of 11andro carbon atoms; and Ac represents the acyl radical of a 20 Stan 3hydrocarbon carboxylic acid of less than 12 carbon atoms. B

18. 11a-N-acetyl-C-homo-androstan-Bfi-ol-17-one. No references cited.

1. A COMPOUND OF THE FOLLOWING FORMULA:
 7. A COMPOUND SELECTED FROM THEGROUP CONSISTING OF THE FOLLOWING FORMULA:
 17. A COMPOUND OF THEFOLLOWING FORMULA:
 19. A COMPOUND SELECTED FROM THE GROUP CONSISTING OFTHOSE OF THE FOLLOWING FORMULA: